Pelvic Organ Prolapse (POP) is a condition of the female pelvic system suffered by a significant proportion of women in the U.S. and more across the globe, every year. POP is caused by the weakening of the pelvic floor muscles and musculo-connective tissues due to child birth, menopause and morbid obesity. Prolapse of the pelvic organs namely the urinary bladder, uterus, and rectum into the vaginal canal can cause vaginal discomfort, strained urination or defecation, and sexual dysfunction. To date, success rates of native tissue POP surgeries vary from 50–70% depending on the definition of cure and time-point of assessment. A better understanding of the mechanics of prolapse may lead to improvement in surgical outcomes. In the current work, the mechanics of progression of anterior and posterior vaginal prolapse were modeled to understand the effect of bladder fill and posterior vaginal stresses using computational approaches. A realistic and full-scale female pelvic system model, comprised of the urinary bladder, vaginal canal, uterus, rectum, and fascial connective tissue, was developed using image segmentation methods. All of the relevant loads and boundary conditions were applied based on a comprehensive study of the anatomy and functional morphology of the female pelvis. Hyperelastic material models were adopted to characterize all pelvic tissues, and a non-linear analysis was invoked. In the first set of simulations, a realistic bladder filling and vaginal tissue stiffening in prolapse were modeled and their effects on the anterior vaginal wall (AVW) were estimated in terms of the induced stresses, strains and displacements. The degree of bladder filling was found to be a strong indicator of stress build-up on the AVW. Also, vaginal tissue stiffening was found to increase the size of the high stress zone on the AVW. The second simulation consisted of modeling the different degrees of posterior vaginal wall (PVW) prolapse, in the presence of an average abdominal pressure. The vaginal length was segmented into four sections to study the localized stresses and strains. Also, a clinically well-known phenomena known as the kneeling effect was observed with the PVW in which the vaginal wall displaces away from the rectum and downward towards the vaginal hiatus. All of these results have relevant clinical implications and may provide important perspective for better understanding the mechanics of POP pathophysiology.